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. 2021;11(3):1285-1296.
doi: 10.3233/JPD-212624.

Mutations in GBA and LRRK2 Are Not Associated with Increased Inflammatory Markers

Avner Thaler  1   2   3   4 , Nurit Omer  1   2   4 , Nir Giladi  1   2   3 , Tanya Gurevich  1   2   3 , Anat Bar-Shira  5 , Mali Gana-Weisz  6 , Orly Goldstein  6 , Meir Kestenbaum  2   7 , Julia C Shirvan  8 , Jesse M Cedarbaum  8   9 , Avi Orr-Urtreger  2   3   6 , Keren Regev  2   10 , Shani Shenhar-Tsarfaty  2   11 , Anat Mirelman  2   3   4
Affiliations

Mutations in GBA and LRRK2 Are Not Associated with Increased Inflammatory Markers

Avner Thaler et al. J Parkinsons Dis. 2021.

Abstract

Background: Inflammation is an integral part of neurodegeneration including in Parkinson's disease (PD). Ashkenazi Jews have high rates of genetic PD with divergent phenotypes among GBA-PD and LRRK2-PD. The role of inflammation in the prodromal phase of PD and the association with disease phenotype has yet to be elucidated.

Objective: To assess central and peripheral cytokines among PD patients with mutations in the LRRK2 and GBA genes and among non-manifesting carriers (NMC) of these mutations in order to determine the role of inflammation in genetic PD.

Methods: The following cytokines were assessed from peripheral blood and cerebrospinal fluid (CSF): TNF-α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10 and INF- γ. A comprehensive intake including general medical conditions, use of anti-inflammatory treatments, motor and cognitive assessments and additional laboratory measures were recorded, enabling the construction of the MDS probable prodromal score.

Results: Data from 362 participants was collected: 31 idiopathic PD (iPD), 30 LRRK2-PD, 77 GBA-PD, 3 homozygote GBA-PD, 3 GBA-LRRK2-PD, 67 LRRK2-NMC, 105 GBA-NMC, 14 LRRK2-GBA-NMC, and 32 healthy controls. No between-group differences in peripheral or CSF cytokines were detected. No correlation between disease characteristics or risk for prodromal PD could be associated with any inflammatory measure.

Conclusion: In this study, we could not detect any evidence on dysregulated immune response among GBA and LRRK2 PD patients and non-manifesting mutation carriers.

Keywords: GBA; LRRK2; Parkinson’s disease; inflammation.

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Conflict of interest statement

AT –Receiving honoraria from Abbvie Israel.

NO –Nothing to disclose

NG –Serves on the Editorial Board of the Journal of Parkinson’s Disease. Serves as consultant to Biogen, Genzyme-Sanofi, Sionara, NeuroDerm, Intec Pharma, Pharma2B, Denali Neuron23 and Abbvie. Receives royalties from Lysosomal Therapeutics (LTI) and payment for lectures from Abbvie, Sanofi-Genzyme, Bial and Movement Disorder Society. Received research support from the Michael J Fox Foundation, the National Parkinson Foundation, the European Union 7th Framework Program, the Israel Science Foundation, Teva NNE program, Biogen, LTI, and Ionis.

TG –Advisory board membership with honoraria from Abbvie, Neuroderm, Medison, Allergan, Cytora and Synnerva, research support from Phonetica Ltd., Israeli Innovation Authority, Sagol School of Neuroscience and Parkinson’s Foundation. Receiving travel support from Abbvie, Allergan, Medisson and Medtronic.

ABS –Nothing to disclose

MGW –Nothing to disclose

OG –Nothing to disclose

MK –Payment for lectures from Abbvie and Teva.

JCS –Employee and shareholder in Biogen, Inc.

JMC –A former employee and shareholder in Biogen, Inc.

AOU –Research support from the Michael J Fox Foundation, Chaya Charitable Fund and Biogen and payment for lectures from Sanofi Genzyme and Pfizer.

KR –Lecture fees and travel grants from Teva, BMS, Biogen, Sanofi Genzyme, Roche, Medison, Novartis and Serono.

SST –Nothing to disclose

AM- Serving as advisor to Neuroderm.

Figures

Fig. 1
Fig. 1
Levels of peripheral cytokines among study participants iPD, idiopathic Parkinson’s disease; NMC, non-manifesting carriers; IL, interleukin; TNF, tumor necrosis factor.
Fig. 2
Fig. 2
Levels of CSF cytokines among study participants iPD, idiopathic Parkinson’s disease; NMC, non-manifesting carriers; IL, interleukin; INF, interferon; TNF, tumor necrosis factor.
See this image and copyright information in PMC

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